Weekly paclitaxel combined with pegylated liposomal doxorubicin (Caelyx™) given every 4 weeks: dose-finding and pharmacokinetic study in patients with advanced solid tumors

Briasoulis, Evangelos; Pentheroudakis, George; Karavasilis, Vasilios; Tzamakou, Eleftheria; Rammou, Dimitra; Pavlidis, Nicholas

doi:10.1093/annonc/mdh404

Cited by 16 publications

(10 citation statements)

References 26 publications

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“…These complex time-and dosedependent tumor priming effects of paclitaxel and the multidimensional drug-drug interactions highlight the need of careful considerations in using paclitaxel in combination therapy. For the combination of paclitaxel and doxorubicin HCl liposomes, the several schedules under clinical evaluation involve using concurrent administration (Campos et al, 2003;Briasoulis et al, 2004). Our current finding that a paclitaxel pretreatment improved the tumor-selective delivery and efficacy of doxorubicin HCl liposomes would support a schedule of administering paclitaxel before doxorubicin HCl liposomes to take advantage of the tumor priming property of paclitaxel.…”

Section: Latexmentioning

confidence: 76%

“…A potential mechanism of the greater tumor delivery of doxorubicin HCl liposomes in the tumor priming group is a reduced doxorubicin clearance by paclitaxel (Briasoulis et al, 2004). This was ruled out because pharmacokinetic results, together with statistical analysis using the bootstrap (see Materials and Methods), indicated that tumor priming did not alter the area under the plasma concentration-time curves of total doxorubicin (sum of free and liposome-entrapped drug).…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Tumor Priming Enhances Delivery and Efficacy of Nanomedicines

Lü

Wientjes²,

Lu³

et al. 2007

J Pharmacol Exp Ther

124

159

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We have shown that high epithelial cell density is a major barrier to the distribution of protein-bound drugs in solid tumors, and tumor priming (expansion of interstitial space using an apoptosis-inducing pretreatment) can promote drug delivery. This study evaluated the optimal conditions of paclitaxel tumor priming (time window, particle size) and its effects on the delivery and efficacy of nanomedicines. Paclitaxel tumor priming was applied to mice bearing human xenograft tumors. The kinetics of paclitaxel-induced apoptosis was evaluated to identify the time window of tumor priming. The effects of tumor priming on the tumor delivery and interstitial dispersion of fluorescence-labeled nanoparticles of various sizes, the perfusion of tumor and normal tissues, the delivery of doxorubicin HCl liposomes to tumor and host tissues, and the antitumor activity and host toxicity were studied. Tumor priming by a single i.v. injection of paclitaxel induced apoptosis, expanded the interstitial space, vessel diameter and blood-perfused area, and promoted the delivery and interstitial dispersion of nanoparticles (100-and 200-nm diameter, administered 48 h after paclitaxel) in a tumor-selective manner. Tumor priming also enhanced the tumor delivery and antitumor activity of doxorubicin HCl liposomes (85 nm) without affecting the delivery to noncancerous host tissues or enhancing host toxicity. Tumor priming represents a potentially useful means to promote tumor-selective delivery and efficacy of nanomedicines. The current study will have significant impact on enhancing delivery and efficacy of nanomedicines and dosing regimen optimization of combination chemotherapy in the clinical setting.

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Section: Latexmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Tumor Priming Enhances Delivery and Efficacy of Nanomedicines

Lü

Wientjes²,

Lu³

et al. 2007

J Pharmacol Exp Ther

124

159

View full text Add to dashboard Cite

show abstract

“…For example, pegylated liposomal doxorubicin has been shown to produce higher plasma levels when coadministered with paclitaxel. 51 However, one should remember that, in the setting of lack of direct confirmatory drug interaction studies of nab-paclitaxel, these interactions are only based on assumption from extrapolation of paclitaxel interactions. Moreover, the drug-drug interaction may not always be clinically relevant (eg, minimal pharmacokinetic changes from clindamycin-paclitaxel combination and minimally increased plasma paclitaxel when given in combination with pazopanib).…”

Section: Gupta Et Almentioning

confidence: 99%

First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

Gupta¹,

Hatoum²,

Dy³

2013

IJN

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Lung cancer is the leading cause of cancer mortality worldwide in both men and women. Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for more than 80% of cases. Paclitaxel has a broad spectrum of activity against various malignancies, including NSCLC. Paclitaxel is poorly soluble in water and thus, until recently, its commercially available preparations contained a non-ionic solvent Cremophor EL®. Cremophor EL® improves the solubility of paclitaxel and allows its intravenous administration. However, certain side-effects associated with paclitaxel, such as hypersensitivity reactions, myelosuppression, and peripheral neuropathy, are known to be worsened by Cremophor®. Nanoparticle albumin-bound paclitaxel ([nab-paclitaxel] ABRAXANE® ABI-007) is a new generation formulation of paclitaxel that obviates the need for Cremophor®, resulting in a safer and faster infusion without requiring the use of premedications to avoid hypersensitivity. Albumin-binding receptor-mediated delivery and lack of sequestering Cremophor® micelles allow higher intratumoral concentration of pharmacologically active paclitaxel. Multiple clinical trials have demonstrated a superior tolerability profile of nab-paclitaxel in comparison to solvent-bound paclitaxel (sb-paclitaxel). A recent Phase III trial compared the effects of weekly nab-paclitaxel in combination with carboplatin versus sb-paclitaxel in combination with carboplatin given every 3 weeks for first line treatment of NSCLC. This trial highlights the weekly nab-paclitaxel combination as an alternate treatment option for NSCLC, with higher response rate in squamous cell NSCLC and longer survival in elderly patients. This review will focus on the properties of nab-paclitaxel and its use in the first line treatment of NSCLC.

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“…In phase I work, PLD was combined with ifosphamide, 58 topotecan (oral 59 or intravenous [60][61][62] ), etoposide, 63 taxanes, [64][65][66][67] platinums, [68][69][70][71] vinorelbine, 24,72 gemcitabine, 73,74 and capecitabine. 75 These trials are reviewed in Table 3, which summarizes the relevant maximum tolerated dose toxicities.…”

Section: Ongoing Development Of Pldmentioning

confidence: 99%

Pegylated liposomal doxorubicin in ovarian cancer

Strother

Matei

2009

TCRM

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Abstract:The encapsulation of doxorubicin in a pegylated liposomal matrix led to a reformulated agent with a different toxicity profile and improved clinical utility. Liposomal doxorubicin is devoid of the cardiac toxicity associated with doxorubicin, but is associated with predictable muco-cutaneous toxicity. The liposomal formulation leads to improved delivery to the target tumor tissue, allowing enhanced uptake by cancer cells. These properties translate into clinical utility in recurrent ovarian cancer as demonstrated by phase II and III trials, this proven clinical efficacy leading to FDA approval in second-line therapy for ovarian cancer. New combinations with cytotoxics, in particular with carboplatin, have demonstrated an acceptable toxicity profile and clinical utility in platinum-sensitive ovarian cancer. A favorable toxicity profile renders liposomal doxorubicin an ideal partner for combination regimens with other cytotoxics, and more recently with biological agents. Such combinations are the subject of ongoing clinical trials.

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Weekly paclitaxel combined with pegylated liposomal doxorubicin (Caelyx™) given every 4 weeks: dose-finding and pharmacokinetic study in patients with advanced solid tumors

Abstract: The combination of PLD/wPTX constitutes an active chemotherapy regimen with mild toxicity that merits investigation in phase II at 30/80 or 35/70 mg/m(2). Patients should be monitored for a potentially increased risk of thromboembolic events.

Cited by 16 publications

References 26 publications

Tumor Priming Enhances Delivery and Efficacy of Nanomedicines

Tumor Priming Enhances Delivery and Efficacy of Nanomedicines

First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel

Pegylated liposomal doxorubicin in ovarian cancer

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Weekly paclitaxel combined with pegylated liposomal doxorubicin (Caelyx™) given every 4 weeks: dose-finding and pharmacokinetic study in patients with advanced solid tumors

Abstract: The combination of PLD/wPTX constitutes an active chemotherapy regimen with mild toxicity that merits investigation in phase II at 30/80 or 35/70 mg/m(2). Patients should be monitored for a potentially increased risk of thromboembolic events.

Cited by 16 publications

References 26 publications

Tumor Priming Enhances Delivery and Efficacy of Nanomedicines

Tumor Priming Enhances Delivery and Efficacy of Nanomedicines

First line treatment of advanced non-small-cell lung cancer &ndash; specific focus on albumin bound paclitaxel

Pegylated liposomal doxorubicin in ovarian cancer

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Product

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About

First line treatment of advanced non-small-cell lung cancer – specific focus on albumin bound paclitaxel